We have continued studies on the oxidation of proteins and specific enzymes in hepatocytes from rats treated with 100% oxygen (oxygen toxicity model) and rats of various ages 3-26 months (aging model). The results show that loss of specific activity of glutamine synthetase (GS) and glucose-6-phosphate dehydrogenase (G-6-PDH) in both models correlates with increased carbonyl content of soluble proteins. Proteases which selectively degrade the oxidized proteins are induced or activated in young rats (3 months) treated with 100% oxygen. However, old rats (26 months) possess only 20% of the selective protease activity of young rats (3 months) and these proteases cannot be induced or activated in response to 100% oxygen treatment. Treatment of young rats with endotoxin (1/40 lethal dose) renders rats tolerant to 100 % oxygen. Moreover, the levels of oxidized proteins in hepatocytes is not increased and enzyme specific activity is not lost. Other studies have been carried out with Dr. Hugh Mickel, Laboratory of Ex- perimental Neuropathology, and Dr. Johanna Moller and Dr. Richard Queries, both of the laboratory of Molecular and Cellular Neurobiology, NINDS, NIH. Previous studies by Norenberg and his colleagues indicated that rapid correction of serum sodium levels following vasopressin-induced hyponatremia leads to highly localized myelinolysis in brains of experimental animals. Rapid correction of serum sodium is also associated with increased protein oxidation of soluble proteins (whole brain) as well as solubilized myelin basic protein (MBP). In vitro experiments also indicate that the major myelin proteins (from normal animals) are highly susceptible to oxidation by various metal catalyzed oxidation (MCO) systems and that the oxidized proteins are readily degraded by Ca(II) activated proteases whereas myelin proteins from control incubations are highly resistant to proteolysis.